Programmed cell death (apoptosis) is critical for the normal development
and homeostasis of the immune system.

There is increasing evidence that
dysregulations of apoptotic pathways are associated with autoimmune disease,
including multiple sclerosis (MS).

Cellular commitment to apoptosis is
partly regulated by the Bcl-2 family proteins, which includes the death
antagonists Bcl-2 and Bcl-X(L), and death agonists Bax and Bad.

Since the
role of these proteins in the pathogenesis of MS is currently unknown,
we analyzed their expression profile in peripheral and intrathecal lymphocytes
from MS patients and appropriate controls.

We observed a significant reduction
in the expression ratios of pro-apoptotic to anti-apoptotic Bcl-2 members
in both peripheral and intrathecal lymphocytes from MS patients when compared
to corresponding ratios in patients with inflammatory or noninflammatory
neurologic controls, or healthy individuals.

The relative coexpression
ratios of these pro- and anti-apoptotic Bcl-2 family proteins in MS were
more significant than the expression of individual members.

Cellular expression of Bcl-2, Bcl-X(L), Bax or
Bad in MS patients was independent of the expression of other apoptotic
regulatory molecules, such as Fas receptor protein or FLIP.

Our findings
suggest that the abnormal expression patterns of Bcl-2 family proteins
in MS may promote apoptotic resistance of potentially pathogenic, autoreactive
lymphocytes, and may allow for continuing cellular proliferation and tissue
destruction within the central nervous system.